Article
Open Access Article

Lenalidomide: A New Agent for Patients With Relapsed or Refractory Multiple Myeloma

Joseph D. Tariman
new therapies, relapse, multiple myeloma
CJON 2007, 11(4), 569-574. DOI: 10.1188/07.CJON.569-574

Lenalidomide is a potent, novel thalidomide analog that has demonstrated promising clinical activity in patients with relapsed or refractory multiple myeloma (MM). It is a lead immunomodulatory drug currently approved by the U.S. Food and Drug Administration. Neutropenia, thrombocytopenia, and thromboembolic events are common adverse effects associated with lenalidomide therapy in patients with MM. Careful monitoring of those known serious adverse effects is essential to prevent life-threatening complications. This article discusses lenalidomide's mechanisms of action, clinical trial results, and the management of common adverse effects in patients with MM.

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    References

    Anderson, K.C. (2005). Lenalidomide and thalidomide: Mechanisms of action—Similarities and differences. Seminars in Hematology, 42(4, Suppl. 4), S3--S8.
    Bennett, C.L., Hussain, Z., Courtney, M., Yarnold, P., Raisch, D., & McKoy, J.M. (2006). RADAR update on thalidomide (Thal) - and lenalidomide (Len)- associated venous thromboembolism (VTE): Safety concerns persist for multiple myeloma (MM) despite FDA approvals in this setting [Abstract # 3310]. Retrieved February 3, 2007, from http://meeting.bloodjournal.org/cgi/content/abstract/108/11/3310?maxtoshow=&HITS=10&hits=10&RESULTFORMAT=1&title=lenalidomide&andorexacttitle=and&andorexacttitleabs=and&andorexactfulltext=and&searchid=1&FIRSTINDEX=0&sortspec=relevance&resourcetype=HWCIT
    Celgene Corporation. (2006a). Revlimid® in combination with dexamethasone sNDA granted approval by FDA for treatment of multiple myeloma. Retrieved January 30, 2007, from http://ir.celgene.com/phoenix.zhtml?c=111960&p=irol-newsArticle&ID=877894&highlight=
    Celgene Corporation. (2006b). Revlimid® (lenalidomide) [Package insert]. Summit, NJ: Author.
    Celgene Corporation. (2006c). Thalomid® sNDA granted FDA approval for treatment of newly diagnosed multiple myeloma. Retrieved January 30, 2007, from http://ir.celgene.com/phoenix.zhtml?c=111960&p=irol-newsArticle&ID=861181&highlight=
    Celgene Corporation. (2006d). Thalomid® (thalidomide) [package insert]. Summit, NJ: Author.
    Celgene Corporation. (2007). Product pipeline. Retrieved July 9, 2007, from http://media.corporate-ir.net/media_files/irol/11/111960/REVISED_20070209Rev_PIPELINE.pdf
    Corral, L.G., Haslett, P.A., Muller, G.W., Chen, R., Wong, L.M., Ocampo, C.J., et al. (1999). Differential cytokine modulation and T cell activation by two distinct classes of thalidomide analogues that are potent inhibitors of TNF-alpha. Journal of Immunology, 163, 380--386.
    Davies, F.E., Raje, N., Hideshima, T., Lentzsch, S., Young, G., Tai, Y.T., et al. (2001). Thalidomide and immunomodulatory derivatives augment natural killer cell cytotoxicity in multiple myeloma. Blood, 98, 210--216.
    Dimopoulos, M.A., Spencer, A., Attal, M., Prince, M., Harousseau, J., Dmoszynska, A., et al. (2005). Study of lenalidomide plus dexamethasone versus dexamethasone alone in relapsed or refractory multiple myeloma (MM): Results of a phase 3 study (MM-010) [Abstract #6]. Blood, 106, 6a.
    Doss, D.S. (2006). Advances in oral therapy in the treatment of multiple myeloma. Clinical Journal of Oncology Nursing, 10, 514--520.
    Dredge, K., Marriott, J.B., Macdonald, C.D., Man, H.W., Chen, R., Muller, G.W., et al. (2002). Novel thalidomide analogues display anti-angiogenic activity independently of immunomodulatory effects. British Journal of Cancer, 87, 1166--1172.
    Gupta, D., Treon, S.P., Shima, Y., Hideshima, T., Podar, K., Tai, Y.T., et al. (2001). Adherence of multiple myeloma cells to bone marrow stromal cells upregulates vascular endothelial growth factor secretion: Therapeutic applications. Leukemia, 15, 1950--1961.
    Hideshima, T., Chauhan, D., Podar, K., Schlossman, R.L., Richardson, P., & Anderson, K.C. (2001). Novel therapies targeting the myeloma cell and its bone marrow microenvironment. Seminars in Oncology, 28, 607--612.
    Hideshima, T., Chauhan, D., Shima, Y., Raje, N., Davies, F.E., Tai, Y.T., et al. (2000). Thalidomide and its analogs overcome drug resistance of human multiple myeloma cells to conventional therapy. Blood, 96, 2943--2950.
    Jemal, A., Siegel, R., Ward, E., Murray, T., Xu, J., & Thun, M.J. (2007). Cancer statistics, 2007. CA: A Cancer Journal for Clinicians, 57(1), 43--66.
    Lentzsch, S., Anderson, G., Kurihara, N., Honjo, T., Anderson, J., Mapara, M.Y., et al. (2005). Thalidomide derivative CC-4047 inhibits inhibits osteoclast formation by down regulation of PU.1 [Abstract #629]. Blood, 106, 187a.
    Lokhorst, H. (2002). Clinical features and diagnostic criteria. In S. Singhal & J. Mehta (Eds.), Myeloma (pp. 151--168). London: Martin Dunitz Ltd.
    Niesvizky, R., Martinez-Banos, D.M., Gelbshtein, U.Y., Cho, H.J., Pearse, R.N., Zafar, F., et al. (2005). Prophylactic low-dose aspirin is effective as antithrombotic therapy in patients receiving combination thalidomide or lenalidomide [Abstract #3454]. Blood, 106, 964a.
    Rajkumar, S.V., Hayman, S.R., Lacy, M.Q., Dispenzieri, A., Geyer, S.M., Kabat, B., et al. (2005). Combination therapy with lenalidomide plus dexamethasone (Rev/Dex) for newly diagnosed myeloma. Blood, 106, 4050--4053.
    Richardson, P., & Anderson, K. (2004). Immunomodulatory analogs of thalidomide: An emerging new therapy in myeloma. Journal of Clinical Oncology, 22, 3212--3214.
    Richardson, P., Jagannath, S., Hussein, M., Berenson, J., Singhal, S., Irwin, D., et al. (2005). A multicenter, single-arm, open-label study to evaluate the efficacy and safety of single-agent lenalidomide in patients with relapsed and refractory multiple myeloma: Preliminary results [Abstract #1565]. Blood, 106, 449a.
    Richardson, P.G., Jagannath, S., Schlossman, R., Zeldenrust, S., Rajkumar, S.V., Alsina, M., et al. (2003). A multi-center, randomized, phase II study to evaluate the efficacy and safety of two CDC-5013 dose regimens when used alone or in combination with dexamethasone (dex) for the treatment of relapsed or refractory multiple myeloma (MM) [Abstract #825]. Blood, 100, 235a.
    Richardson, P.G., Schlossman, R.L., Weller, E., Hideshima, T., Mitsiades, C., Davies, F., et al. (2002). Immunomodulatory drug CC-5013 overcomes drug resistance and is well tolerated in patients with relapsed multiple myeloma. Blood, 100, 3063--3067.
    Singhal, S., Mehta, J., Desikan, R., Ayers, D., Roberson, P., Eddlemon, P., et al. (1999). Antitumor activity of thalidomide in refractory multiple myeloma. New England Journal of Medicine, 341, 1565--1571.
    Streetly, M.J., Gyertson, K., Kazmi, M., Zeldis, J., & Schey, S.A. (2007). Prolonged survival with actimid (CC-4047) [Abstract PO-643]. Haematologica, 92(Suppl. 2), 166.
    Tariman, J.D. (2003a). Thalidomide: Current therapeutic uses and management of its toxicities. Clinical Journal of Oncology Nursing, 7, 143--147.
    Tariman, J.D. (2003b). Understanding novel therapeutic agents for multiple myeloma. Clinical Journal of Oncology Nursing, 7, 521--528.
    Tariman, J.D., & Estrella, S.M. (2005). The changing treatment paradigm in patients with newly diagnosed multiple myeloma: Implications for nursing [Online exclusive]. Oncology Nursing Forum, 32, E127--E138. Retrieved July 3, 2007, from http://www.ons.org/publications/journals/ONF/volume32/issue6/32061098.asp
    Weber, D.M., Chen, C., Niesvizky, R., Wang, M., Belch, A., Stadtmauer, E., et al. (2006). Lenalidomide plus high-dose dexamethasone provides improved overall survival compared to high-dose dexamethasone alone for relapsed or refractory multiple myeloma (MM): Results of a North American phase III study (MM-009) [Abstract # 7521]. Journal of Clinical Oncology, 24(18s). Retrieved February 2, 2007, from http://www.asco.org/portal/site/ASCO/menuitem.34d60f5624ba07fd506fe310ee37a01d/?vgnextoid=76f8201eb61a7010VgnVCM100000ed730ad1RCRD&vmview=abst_detail_view&confID=40&index=y&abstractID=34363
    Zangari, M., Tricot, G., Zeldis, J., Eddlemon, P., Saghafifar, F., & Barlogie, B. (2001). Results of phase 1 study of CC-5013 for the treatment of multiple myeloma (MM) patients who relapse after high dose chemotherapy (HDCT) [Abstract # 3226]. Blood, 98, 775a.
    Zeldis, J.B., Williams, B.A., Thomas, S.D., & Elsayed, M.E. (1999). S.T.E.P.S.: A comprehensive program for controlling and monitoring access to thalidomide. Clinical Therapeutics, 21, 319--330.
    Zonder, J.A., Durie, B.G.M., McCoy, J., Crowley, J., Zeldis, J.B., Ghannam, L., et al. (2005). High incidence of thrombotic events observed in patients receiving lenalidomide (L) + dexamethasone (D) (LD) as first-line therapy for multiple myeloma (MM) without aspirin (ASA) prophylaxis [Abstract #3455]. Blood, 106, 964a.